Search results for: prognostic markers

Authors: H. Oudira, A. Saifi

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The therapeutic utility of certain Auger emitters such as iodine-125 depends on their position within the cell nucleus . Or diagnostically, and to maintain as low as possible cell damage, it is preferable to have radionuclide localized outside the cell or at least the core. One solution to this problem is to consider markers capable of conveying anticancer drugs to the tumor site regardless of their location within the human body. The objective of this study is to simulate the impact of a complex such as bleomycin on single and double strand breaks in the DNA molecule. Indeed, this simulation consists of the following transactions: - Construction of BLM -Fe- DNA complex. - Simulation of the electron’s transport from the metastable state excitation of Fe 57 by the Monte Carlo method. - Treatment of chemical reactions in the considered environment by the diffusion equation. For physical, physico-chemical and finally chemical steps, the geometry of the complex is considered as a sphere of 50 nm centered on the binding site , and the mathematical method used is called step by step based on Monte Carlo codes.

Keywords: concentration, yield, radical species, bleomycin, excitation, DNA

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Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Rupak Kumar Sarma, Ratul Saikia

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Macrophytes encompass major functional group in eutrophic wetland ecosystems. As a key functional element of freshwater lakes, they play a crucial role in regulating various wetland biogeochemical cycles, as well as maintain the biodiversity at the ecosystem level. The high carbon-rich underground biomass of macrophyte populations may harbour diverse microbial community having significant potential in maintaining different biogeochemical cycles. The present investigation was designed to study the macrophyte-microbe interaction in coupled nitrification and denitrification, considering Deepor Beel Lake (a Ramsar conservation site) of North East India as a model eutrophic system. Highly eutrophic sites of Deepor Beel were selected based on sediment oxygen demand and inorganic phosphorus and nitrogen (P&N) concentration. Sediment redox potential and depth of the lake was chosen as the benchmark for collecting the plant and sediment samples. The average highest depth in winter (January 2016) and summer (July 2016) were recorded as 20ft (6.096m) and 35ft (10.668m) respectively. Both sampling depth and sampling seasons had the distinct effect on variation in macrophyte community composition. Overall, the dominant macrophytic populations in the lake were Nymphaea alba, Hydrilla verticillata, Utricularia flexuosa, Vallisneria spiralis, Najas indica, Monochoria hastaefolia, Trapa bispinosa, Ipomea fistulosa, Hygrorhiza aristata, Polygonum hydropiper, Eichhornia crassipes and Euryale ferox. There was a distinct correlation in the variation of major sediment physicochemical parameters with change in macrophyte community compositions. Quantitative estimation revealed an almost even accumulation of nitrate and nitrite in the sediment samples dominated by the plant species Eichhornia crassipes, Nymphaea alba, Hydrilla verticillata, Vallisneria spiralis, Euryale ferox and Monochoria hastaefolia, which might have signified a stable nitrification and denitrification process in the sites dominated by the selected aquatic plants. This was further examined by a systematic analysis of microbial populations through culture dependent and independent approach. Culture-dependent bacterial community study revealed the higher population of nitrifiers and denitrifiers in the sediment samples dominated by the six macrophyte species. However, culture-independent study with bacterial 16S rDNA V3-V4 metagenome sequencing revealed the overall similar type of bacterial phylum in all the sediment samples collected during the study. Thus, there might be the possibility of uneven distribution of nitrifying and denitrifying molecular markers among the sediment samples collected during the investigation. The diversity and abundance of the nitrifying and denitrifying molecular markers in the sediment samples are under investigation. Thus, the role of different aquatic plant functional types in microorganism mediated nitrogen cycle coupling could be screened out further from the present initial investigation.

Keywords: denitrification, macrophyte, metagenome, microorganism, nitrification

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Authors: Paul Rowley, Adam Thirkill, Nick Doylend, Philip Leicester, Becky Gough

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The dynamic performance of all energy generation technologies is impacted to varying degrees by the stochastic properties of the wider system within which the generation technology is located. This stochasticity can include the varying nature of ambient renewable energy resources such as wind or solar radiation, or unpredicted changes in energy demand which impact upon the operational behaviour of thermal generation technologies. An understanding of these stochastic impacts are especially important in contexts such as highly distributed (or embedded) generation, where an understanding of issues affecting the individual or aggregated performance of high numbers of relatively small generators is especially important, such as in ESCO projects. Probabilistic evaluation of monitored or simulated performance data is one technique which can provide an insight into the dynamic performance characteristics of generating systems, both in a prognostic sense (such as the prediction of future performance at the project’s design stage) as well as in a diagnostic sense (such as in the real-time analysis of underperforming systems). In this work, we describe the development, application and outcomes of a new approach to the acquisition of datasets suitable for use in the subsequent performance and impact analysis (including the use of Bayesian approaches) for a number of distributed generation technologies. The application of the approach is illustrated using a number of case studies involving domestic and small commercial scale photovoltaic, solar thermal and natural gas boiler installations, and the results as presented show that the methodology offers significant advantages in terms of plant efficiency prediction or diagnosis, along with allied environmental and social impacts such as greenhouse gas emission reduction or fuel affordability.

Keywords: renewable energy, dynamic performance simulation, Bayesian analysis, distributed generation

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Authors: Imdad Ullah Khan, Yongseok Yoon, Kyeung Uk Choi, Kwang Rae Jo, Namyul Kim, Eunbee Lee, Wan Hee Kim, Oh-Kyeong Kweon

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The primary spinal cord injury (SCI) causes mechanical damage to the neurons and blood vessels. It leads to secondary SCI, which activates multiple pathological pathways, which expand neuronal damage at the injury site. It is characterized by vascular disruption, ischemia, excitotoxicity, oxidation, inflammation, and apoptotic cell death. It causes nerve demyelination and disruption of axons, which perpetuate a loss of impulse conduction through the injured spinal cord. It also leads to the production of myelin inhibitory molecules, which with a concomitant formation of an astroglial scar, impede axonal regeneration. The pivotal role regarding the neuronal necrosis is played by oxidation and inflammation. During an early stage of spinal cord injury, there occurs an abundant expression of reactive oxygen species (ROS) due to defective mitochondrial metabolism and abundant migration of phagocytes (macrophages, neutrophils). ROS cause lipid peroxidation of the cell membrane, and cell death. Abundant migration of neutrophils, macrophages, and lymphocytes collectively produce pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), matrix metalloproteinase, superoxide dismutase, and myeloperoxidases which synergize neuronal apoptosis. Therefore, it is crucial to control inflammation and oxidation injury to minimize the nerve cell death during secondary spinal cord injury. Therefore, in response to oxidation and inflammation, heme oxygenase-1 (HO-1) is induced by the resident cells to ameliorate the milieu. In the meanwhile, neurotrophic factors are induced to promote neuroregeneration. However, it seems that anti-stress enzyme (HO-1) and neurotrophic factor (BDNF) do not significantly combat the pathological events during secondary spinal cord injury. Therefore, optimum healing can be induced if anti-inflammatory and neurotrophic factors are administered in a higher amount through an exogenous source. During the first experiment, the inflammation and neuroregeneration were selectively targeted. HO-1 expressing MSCs (HO-1 MSCs) and BDNF expressing MSCs (BDNF MSC) were co-transplanted in one group (combination group) of dogs with subacute spinal cord injury to selectively control the expression of inflammatory cytokines by HO-1 and induce neuroregeneration by BDNF. We compared the combination group with the HO-1 MSCs group, BDNF MSCs group, and GFP MSCs group. We found that the combination group showed significant improvement in functional recovery. It showed increased expression of neural markers and growth-associated proteins (GAP-43) than in other groups, which depicts enhanced neuroregeneration/neural sparing due to reduced expression of pro-inflammatory cytokines such as TNF-alpha, IL-6 and COX-2; and increased expression of anti-inflammatory markers such as IL-10 and HO-1. Histopathological study revealed reduced intra-parenchymal fibrosis in the injured spinal cord segment in the combination group than in other groups. Thus it was concluded that selectively targeting the inflammation and neuronal growth with the combined use of HO-1 MSCs and BDNF MSCs more favorably promote healing of the SCI. HO-1 MSCs play a role in controlling the inflammation, which favors the BDNF induced neuroregeneration at the injured spinal cord segment of dogs.

Keywords: HO-1 MSCs, BDNF MSCs, neuroregeneration, inflammation, anti-inflammation, spinal cord injury, dogs

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Authors: Azar Heidarizadi, Mahdieh Salimi, Hossein Mozdarani

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Introduction: As a complex disease, breast cancer results from several genetic and epigenetic changes. Lactoferrin, a member of the transferrin family, is reported to have a number of biological functions, including DNA synthesis, immune responses, iron transport, etc., any of which could play a role in tumor progression. The aim of this study was to investigate the bioinformatics data and experimental assay to find the pattern of promoter methylation and gene expression of LTF in breast cancer in order to study its potential role in cancer management. Material and Methods: In order to evaluate the methylation status of the LTF promoter, we studied the MS-PCR and Real-Time PCR on samples from patients with breast cancer and normal cases. 67 patient samples were conducted for this study, including tumoral, plasma, and normal tissue adjacent samples, as well as 30 plasma from normal cases and 10 tissue breast reduction cases. Subsequently, bioinformatics analyses such as cBioPortal databases, string, and genomatix were conducted to disclose the prognostic value of LTF in breast cancer progression. Results: The analysis of LTF expression showed an inverse relationship between the expression level of LTF and the stages of tissues of breast cancer patients (p<0.01). In fact, stages 1 and 2 had a high expression in LTF, while, in stages 3 and 4, a significant reduction was observable (p < 0.0001). LTF expression frequently alters with a decrease in the expression in ER⁺, PR⁺, and HER2⁺ patients (P < 0.01) and an increase in the expression in the TNBC, LN¯, ER¯, and PR- patients (P < 0.001). Also, LTF expression is significantly associated with metastasis and lymph node involvement factors (P < 0.0001). The sensitivity and specificity of LTF were detected, respectively. A negative correlation was detected between the results of level expression and methylation of the LTF promoter. Conclusions: The altered expression of LTF observed in breast cancer patients could be considered as a promotion in cell proliferation and metastasis even in the early stages of cancer.

Keywords: LTF, expression, methylation, breast cancer

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Ravinder Kaur

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Introduction Global cerebrovascular reactivity (CVR) mapping is a promising clinical assessment for stress-testing the brain using physiological challenges, such as CO₂, to elicit changes in perfusion. It enables real-time assessment of cerebrovascular integrity and health. Conventional imaging approaches solely use steady-state parameters, like cerebral blood flow (CBF), to evaluate the integrity of the resting parenchyma and can erroneously show a healthy brain at rest, despite the underlying pathogenesis in the presence of cerebrovascular disease. Conversely, coupling CO₂ inhalation with phase-contrast MRI neuroimaging interrogates the capacity of the vasculature to respond to changes under stress. It shows promise in providing prognostic value as a novel health marker to measure neurovascular function in disease and to detect early brain vasculature dysfunction. Objective This exploratory study was established to:(a) quantify the CBF response to CO₂ in hypocapnia and hypercapnia,(b) evaluate disparities in CVR between internal carotid (ICA) and vertebral artery (VA), and (c) assess sex-specific variation in CVR. Methodology Phase-contrast MRI was employed to measure the cerebrovascular reactivity to CO₂ (±10 mmHg). The respiratory interventions were presented using the prospectively end-tidal targeting RespirActTM Gen3 system. Post-processing and statistical analysis were conducted. Results In 9 young, healthy subjects, the CBF increased from hypocapnia to hypercapnia in all vessels (4.21±0.76 to 7.20±1.83 mL/sec in ICA, 1.36±0.55 to 2.33±1.31 mL/sec in VA, p < 0.05). The CVR was quantitatively higher in ICA than VA (slope of linear regression: 0.23 vs. 0.07 mL/sec/mmHg, p < 0.05). No statistically significant effect was observed in CVR between male and female (0.25 vs 0.20 mL/sec/mmHg in ICA, 0.09 vs 0.11 mL/sec/mmHg in VA, p > 0.05). Conclusions The principal finding in this investigation validated the modulation of CBF by CO₂. Moreover, it has indicated that regional heterogeneity in hemodynamic response exists in the brain. This study provides scope to standardize the quantification of CVR prior to its clinical translation.

Keywords: cerebrovascular disease, neuroimaging, phase contrast MRI, cerebrovascular reactivity, carbon dioxide

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Authors: James M. Geidner

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Objective: The purpose of this meta-analysis was to examine the evidence for the effectiveness of exercise interventions on reducing metabolic components in children and/or adolescents diagnosed with Paediatric Metabolic Syndrome. Methods: A computerized search was made from four databases: PubMed, PsycInfo, SPORTDiscus, Cochrane Central Register. The analysis was restricted to children and adolescents with metabolic syndrome examining the effect of exercise interventions on metabolic components. Effect size and 95% confidence interval were calculated and the heterogeneity of the studies was estimated using Cochran’s Q-statistic and I2. Bias was assessed using multiple tools and statistical analyses. Results: Thirteen studies, consisting of 19 separate trials, were selected for the meta-analysis as they fulfilled the inclusion criteria (n=908). Exercise interventions resulted in decreased waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, insulin resistance, triglycerides, and High-Density Lipoprotein Cholesterol (HDL-C). Conclusions: This meta-analysis provides insights into the effectiveness of exercise interventions on markers of Paediatric Metabolic Syndrome in children and adolescents.

Keywords: metabolic syndrome, syndrome x, pediatric, meta-analysis

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Authors: Tamar Beridze, Elisa Boscari, Fleur Scheele, Tamari Edisherashvili, Cort Anderson, Leonardo Congiu

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The eastern part of the Black Sea and its tributaries are suitable habitats for several sturgeon species, among which Acipenser gueldenstaedtii, A. stellatus, A. nudiventris, A. persicus, A. sturio, and H. huso are well documented. However, different threats have led these species to a dramatic decline; all of them are currently listed as Critically Endangered and some Locally Extinct in that area. We tested 94 wild sturgeon samples from the Black Sea and Rioni River by analyzing the mitochondrial Control Region and nuclear markers for hybrid identification. The data analyses (1) assessed mitochondrial diversity among samples, (2) identified their species, as well as (3) indicated instances of hybridization. The data collected, besides confirming a sharp decrease of catches of Beluga and Stellate sturgeon in recent years, also revealed four juvenile hybrids between Russian and Stellate sturgeon, providing the first evidence of natural interspecific hybridization in the Rioni. The present communication raises concerns about the status of sturgeon species in this area and underlines the urgent need for conservation programs to restore self-sustaining populations.

Keywords: black sea, sturgeon, Rioni river, interspecific hybridization

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Junfeng Yan, Wenkui Hou

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Prognostics and Health Management (PHM) is a technology to monitor the equipment status and predict impending faults. It is used to predict the potential fault and provide fault information and track trends of system degradation by capturing characteristics signals. So how to detect characteristics signals is very important. The select of test point plays a very important role in detecting characteristics signal. Traditionally, we use dependency model to select the test point containing the most detecting information. But, facing the large complicated system, the dependency model is not built so easily sometimes and the greater trouble is how to calculate the matrix. Rely on this premise, the paper provide a highly effective method to select test point without dependency model. Because signal flow model is a diagnosis model based on failure mode, which focuses on system’s failure mode and the dependency relationship between the test points and faults. In the signal flow model, a fault information can flow from the beginning to the end. According to the signal flow model, we can find out location and structure information of every test point and module. We break the signal flow model up into serial and parallel parts to obtain the final relationship function between the system’s testability or prediction metrics and test points. Further, through the partial derivatives operation, we can obtain every test point’s importance degree in determining the testability metrics, such as undetected rate, false alarm rate, untrusted rate. This contributes to installing the test point according to the real requirement and also provides a solid foundation for the Prognostics and Health Management. According to the real effect of the practical engineering application, the method is very efficient.

Keywords: false alarm rate, importance degree, signal flow model, undetected rate, untrusted rate

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Authors: Fatmawati Adam, Saidatul Syaima Mat Tari, Saiful Nizam Tajuddin, Nurul Salwa Azliyana Hamzah

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Essential oil of agarwood or known as Gaharu in Malay is highly prized for its value as luxury fragrances and incense. However, the complexities of the chemical composition of agarwood itself is the main challenge for establishment of an effective recovery method, which is able to ensure uniform qualities and standard for each batch of essential oil production. Agarwood markers are actually a blend of volatile and non-volatile compounds. While volatile molecules could be easily retrieved by the present distillation technique, the high solubility properties are the limiting factor for the latter. With regard to this, an elementary chemistry resolution study had been performed on commercial agarwood essential oil-water mixture, by the application of preparative HPLC and FTIR. Interpretation of the results leads to the theoretical postulation that, agarwood water mixture comprise of agarospirol, jinkohol, jinkoh eremol and khusenol. This study provides a pinpoint on the chemical characteristics of water soluble (non-volatile) agarwood compounds, therefore, will be an insight for researchers to develop a more strategic technique for their extraction. Thereafter the optimum quality of this essential oil could be controlled in a more improved way.

Keywords: Agarwood, Aquillaria Malaccensis, agarospirol, jinkohol, jinkoh eremol, khusenol

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Ozhan Simsek, Dicle Donmez, Burhanettin Imrak, Ahsen Isik Ozguven, Yildiz Aka Kacar

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Pomegranate (Punica granatum L.) is known to be one of the oldest edible fruit tree species, with a wide geographical global distribution. Fruits from the two defined varieties (Hicaznar and 33N26) were taken at intervals after pollination and fertilization at different sizes. Seed samples were used for transcriptome sequencing. Primary sequencing was produced by Illumina Hi-Seq™ 2000. Firstly, we had raw reads, and it was subjected to quality control (QC). Raw reads were filtered into clean reads and aligned to the reference sequences. De novo analysis was performed to detect genes expressed in seeds of pomegranate varieties. We performed downstream analysis to determine differentially expressed genes. We generated about 27.09 gb bases in total after Illumina Hi-Seq sequencing. All samples were assembled together, we got 59,264 Unigenes, the total length, average length, N50, and GC content of Unigenes are 84.547.276 bp, 1.426 bp, 2,137 bp, and 46.20 %, respectively. Unigenes were annotated with 7 functional databases, finally, 42.681(NR: 72.02%), 39.660 (NT: 66.92%), 30.790 (Swissprot: 51.95%), 20.212 (COG: 34.11%), 27.689 (KEGG: 46.72%), 12.328 (GO: 20.80%), and 33,833 (Interpro: 57.09%) Unigenes were annotated. With functional annotation results, we detected 42.376 CDS, and 4.999 SSR distribute on 16.143 Unigenes.

Keywords: next generation sequencing, SSR, RNA-Seq, Illumina

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Muhammad Tarmidzi, Reza M. G. Gani, Andri Luthfi

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The purpose of this study is to identify rock zone containing hydrocarbons with calculating rock property includes volume shale, total porosity, effective porosity and water saturation. Identification method rock property based on GR log, resistivity log, neutron log and density rock. Zoning is based on sequence stratigraphic markers that are sequence boundary (SB), transgressive surface (TS) and flooding surface (FS) which correlating ten well log in blok “M”. The results of sequence stratigraphic correlation consist of eight zone that are two LST zone, three TST zone and three HST zone. The result of rock property calculation in each zone is showing two LST zone containing hydrocarbons. LST-1 zone has average volume shale (Vsh) 25%, average total porosity (PHIT) 14%, average effective porosity (PHIE) 11% and average water saturation 0,83. LST-2 zone has average volume shale (Vsh) 19%, average total porosity (PHIT) 21%, average effective porosity (PHIE) 17% and average water saturation 0,82.

Keywords: hydrocarbons zone, petrophysic, rock property, sequence stratigraphic

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Authors: Muhammad Mohsan, Mehboob Ur-Rahman, Sana Zulfiqar, Shumila Ashfaq

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Brown Rust (Puccinia triticina), also known as leaf rust, pose a serious threat to wheat cultivation in the world. Nine candidate wheat lines/mutants were subjected to rust inoculation, lodging and aphid population in vivo conditions. Four lines/mutants (E-284, E-505, 2008-6 MR and 2008-14MR) were found resistant to leaf rust attack. Two lines (PGMB 15-29 and 2011-1 MR) displayed moderately resistant reactions against the disease. Three lines/mutants were depicted as susceptible to leaf rust. The lowest population of aphids, i.e., 16.67, was observed on 2008-14MR. Three lines/mutants (NN1-47, NN1-89 and PGMB 15-29) were found under zero level of lodging. The presence and absence of different leaf rust-resistant genes like Lr13, Lr34, Lr46 and Lr67 were assessed with the help of molecular markers. All the wheat lines/mutants were found loaded with leaf rust-resistant genes such as Lr13 and Lr 34, while Lr46 and Lr67 were found in 66% of wheat lines/mutants. The resistant source can be exploited in the breeding program to develop rust, aphid and lodging with race-nonspecific resistant wheat variety.

Keywords: wheat, leaf rust, lodging, aphid

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Authors: Yusra Pintaningrum, Ilma Fahira Basyir, Sony Hilal Wicaksono, Vito A. Damay

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Background: Coronary artery calcium (CAC) scores play an important role in improving prognostic accuracy and can be selectively used to guide the allocation of statin therapy for atherosclerotic cardiovascular disease outcomes and potentially associated with the occurrence of MACE (Major Adverse Cardiovascular Event) and MI (Myocardial Infarction). Objective: This systematic review and meta-analysis aim to analyze the findings of a study about CAC Score and statin treatment effect on MI and MACE risk. Methods: Search for published scientific articles using the PRISMA (Preferred Reporting, Items for Systematic Reviews and Meta-Analysis) method conducted on PubMed, Cochrane Library, and Medline databases published in the last 20 years on “coronary artery calcium” AND “statin” AND “cardiovascular disease” Further systematic review and meta-analysis using RevMan version 5.4 were performed based on the included published scientific articles. Results: Based on 11 studies included with a total of 1055 participants, we performed a meta-analysis and found that individuals with CAC score > 0 increased risk ratio of MI 8.48 (RR = 9.48: 95% CI: 6.22 – 14.45) times and MACE 2.48 (RR = 3.48: 95% CI: 2.98 – 4.05) times higher than CAC score 0 individual. Statin compared against non-statin treatment showed a statistically insignificant overall effect on the risk of MI (P = 0.81) and MACE (P = 0.89) in an individual with elevated CAC score 1 – 100 (P = 0.65) and > 100 (P = 0.11). Conclusions: This study found that an elevated CAC scores individual has a higher risk of MI and MACE than a non-elevated CAC score individual. There is no significant effect of statin compared against non-statin treatment to reduce MI and MACE in elevated CAC score individuals of 1 – 100 or > 100.

Keywords: coronary artery calcium, statin, cardiovascular disease, myocardial infarction, MACE

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Authors: Ghorbeli Eya, Naija Lamia, Khessairi Nayssem, Saadallah Fatma, Slimane Maher, Tarek Ben Dhiab

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INTRODUCTION: Borderline ovarian tumors account for 15 to 20% of ovarian tumors. Prognostic factors of recurrence include the stage of the disease, presence of peritoneal implants, micropapillary pattern, microinvasion and intra-epithelial carcinoma. Fertility sparing constitutes a major therapeutic issue in young patients that leads to conservative surgical treatment in specific cases. METHODS: We conducted a retrospective descriptive study including patients treated at the Salah Azaiez Institute for Borderline Ovarian Tumor who underwent conservative surgical treatment from 2003 to 2018. RESULTS: Nine patients were included in our study. The median age was 33 years. Three patients were nulliparous. Given the age, conservative treatment was indicated in all these patients. Cystectomy without ovariectomy was indicated in 5 of the 9 women, which was within the margin of tumor resection on definitive anatomopathic examination in 3 of the 5 women. In contrast, given the impossibility of ovarian conservation, total annexectomy was carried out in 4 of all these women. All of the patients were followed regularly postoperatively; three had a carcinomatous transformation as an ovarian adenocarcinoma at an average interval of 18 months. Among these three patients, a single one presented intra-peritoneal metastases, requiring radical surgical treatment and adjuvant chemotherapy with 6 cures of Carbo-Taxol, with a good tolerance and a complete response. Moreover, one patient had a recurrence on the contralateral ovary as a Borderline mucinous ovarian tumor. For the remaining four women, after a median follow-up of 35 months, one patient fell spontaneously pregnant during follow-up, and three patients were in complete remission at 16 months. CONCLUSION: Borderline tumors of the ovary usually occur in young patients, which makes conservative treatment advisable if possible, but this always comes with a risk of recurrence and/or carcinomatous transformation, especially if the conservative surgical procedure was a cystectomy instead of a total annexectomy, and even more so if the resection margins were tumoral.

Keywords: ovarian tumor, conservative treatment, surgical management, borderline ovarian tumor, recurrence management

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Authors: Aliakbar Hafezi, Jalal Taherian, Jamshid Abedi, Mahsa Elahi

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Background: Bones are commonly affected by renal cell carcinoma (RCC) (primarily or secondary), and this condition causes bone fragility. The aim of this study was to evaluate the diagnostic value of noninvasive methods for the diagnosis of ROD in RCC patients on hemodialysis (HD) in northern Iran. Methods: In this cross-sectional study, 50 RCC patients with ESRD referred to dialysis units in northern Iran during 2021-2024 were randomly selected and investigated. The biochemical and radiographic evaluation of ROD and its subtypes was performed, and then all patients underwent bone biopsy and histopathological study, and finally, the diagnostic value of the noninvasive methods was assessed. Results: The mean age of patients was 58.9 ± 11.7 years, and 27 cases (54.0%) were female. 38 (76.0%) of RCC patients with ESRD had ROD, and 12 patients (24.0%) had no evidence of bone disorders. The sensitivity, specificity, positive and predictive values and accuracy of the noninvasive methods for the diagnosis of ROD were 92%, 82%, 95%, 75% and 90%, respectively. Conclusion: This study showed that the frequency of ROD in RCC patients with ESRD in northern Iran was high and the biochemical and radiographic markers have a high diagnostic value for ROD as well as histopathological assessment.

Keywords: renal cell carcinoma, renal osteodystrophy, hemodialysis, non-metastatic

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Authors: Farouk A. N. Bouhadiba

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This work addresses the issue of the LMD(Licence, Master, Doctorat) in Algeria and the impact it has had on education quality in terms of educational affect and effect. It starts with a brief introduction to the financial means, the educational settings, and the social environment in place when the LMD was institutionalized in Algeria (2003-2004). Some factors for the success or failure of this top-down institutional endeavor are examined and analyzed. These include – among other factors - the teacher/student attitudes, apprehensions, and motivations on the one hand and the institutional euphoria for the LMD in Algeria on the other hand. Some issues at stake are discussed. More specifically, the professional versus the student affect on today’s attitudes, interests, and values is examined as a result of nearly two decades of LMD teaching and learning in Algerian universities. We shall then present some official curricula that, in terms of content, reflect the spirit, principles, and architectures of the LMD but which, in reality, are partially, if not fully, set aside when it comes to teaching practices, learning behaviors, motivation, and evaluation. The discussion on effect highlights attitudinal, developmental, and social markers that are indicative of the extent to which Education Quality in Algeria has been positively or negatively affected by the implementation of the LMD.

Keywords: LMD bachelor's masters doctorat, affects and effects, education quality, Algeria

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Authors: Diriba Dereje

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Background: Cardiac and renal disease are the most prevalent chronic non-communicable diseases (CNCD) affecting the community in a significant manner. The best and recommended method in halting CNCD is by working on prevention as early as possible. This is only possible if early surrogate markers are identified. As part of the stated solution, this study will identify an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Objective: The main aim of this study was to assess an association between microalbuminuria (an early surrogate marker of renal and cardiac disease) and lung function test among adult in the community. Methodology: Community based cross sectional study was conducted among 384 adult in Jimma town. A systematic sampling technique was used in selecting participants to the study. In searching for the possible association, binary and multivariate logistic regression and t-test was conducted. Finally, the association between microalbuminuria and lung function test was well stated in the form of figures and written description. Result and Conclusion: A significant association was found between microalbuminuria and different lung function test parameters.

Keywords: microalbuminuria, lung function, association, test

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Authors: Dilani Wimalasiri, Robert Brkljaca, Sylvia Urban, Terrence Piva, Tien Huynh

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Momordica cochinchinensis (Cucurbitaceae) is used as food and traditional medicine in South East Asia and is commonly known as Red Gac. The fruit aril consists 70 times higher lycopene and 10 times higher β-carotene than all known fruits and vegetables. Despite its nutritional value there is little information available on its genetic variation and its influence on nutritional value. In this study; genetic and nutritional variation (lycopene and β-carotene) was investigated among 47 M. cochinchinensis samples collected from Australia, Thailand and Vietnam using molecular markers (RAPD and ISSR) and HPLC, respectively. UPGMA based cluster analysis of genetic data grouped Northern and Central Vietnam samples together but were separated from Australia, Thailand and Southern Vietnam samples. The concentration of lycopene was significantly higher among the samples collected from Central Vietnam (p<0.05) and the concentration of β-carotene was significantly higher among the samples collected from Northern Vietnam (p<0.05) indicating the existence of best varieties. This study provides vital information in genetic diversity and facilitates the selection and breeding for nutritious M. cochinchinensis varieties.

Keywords: momordica cochinchinensis, lycopene, beta carotene, genetic diversity

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Authors: Ajay Gogia, Svs Deo, Dn Sharma, Atul Batra, Ashutash Mishra

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Background and Aims: Breast cancer in women aged less than 25 years (defined as very young breast cancer, VYBC) is rare and accounts for 0.25% of all breast cancer in the West. There is no data available on VYBC from developing countries. The aim of this study was to analyze the clinical, pathological, and prognostic factors and outcomes in VYBC. Methods: This retrospective analysis was performed on 80 patients aged 25 years or less (screened 8000 files of female BC) who were registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India, over a 15-year period between 2011 and 2023. Results: The median age was 21.5 years (range 16-25). A positive family history (siblings and parents) was elicited in 30% of cases, and breast cancer gene (BRCA1/2) mutation was found in 33% of cases patients. Ten patients (12.5%) patients have pregnancy-associated breast cancer (BC detected during pregnancy or 1 year after postpartum period). The TNM stage distribution was Stage I was 0, stage II -30%, stage III –60% and Stage IV -10 %patients. Seventy percent of tumors were high grade, and 90% had pathological node-positive disease. Estrogen, Progesterone, and human epidermal growth factor receptor 2 (HER2)/neu positivity were 25%,25% and 35%, respectively. Triple-negative breast cancer constituted 40% of patients. With a median follow-up of 42 months, 3 years, relapse-free survival (nonmetastatic disease), progression-free survival (metastatic disease) and overall survival were 30%, 15% and 50%, respectively. Conclusions: Very young women constituted 1% of all breast cancer cases. Advanced disease at presentation and high-risk pathological features result in poor outcomes. One-third of VYBCs are associated with BRCA mutation, which requires genetic counseling and risk reduction surgery if required. Due to the aggressive behavior of BC in this age group, need early diagnosis and prompt treatment

Keywords: very young, breast cancer, outcome, developing country, India

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Authors: Aniruddha Kulkarni

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In very few cases of external hernias we require imaging modalities as on most occasions clinical examination tests are good enough. Ultrasound will help in chronic abdominal or groin pain, equivocal clinical results & complicated hernias. Ultrasound is useful in assessment of cause of raised intrabdominal pressure. In certain cases will comment about etiology, complications and chronicicty of lesion. Screening of rest of abdominal organs too is important advantage being real time modality. Cost effectiveness, no radiation allows modality be used repeatedly in indicated cases. Sonography is better accepted by patients too as it is cost effective. Best advanced tissue harmonic equipment and increasing expertise making it popular. Ultrasound can define surgical anatomy, rent size, contents, etiological /recurrence factors in great detail and with authority hence accidental findings in a planned surgical procedure can be easily avoided. Clinical dynamic valselva and reducibility test can better documented by real time ultrasound study. In case of recurrence, Sonography will help in assessing the hernia details better as being dynamic real time investigation. Ultrasound signs in case of internal hernias are well comparable with CT findings.

Keywords: laparoscopic repair, Hernia, CT findings, chronic pain

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Authors: Amer Elgerwi, Abdelrazzag El-Magdoub, Abubakr El-Mahmoudy

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There are many bacterial infections affecting sheep that necessitates antibiotic intervention. Amoxicillin is among commonly used antibiotics in such case for its broad spectrum of activity. However, the side alterations in blood and organ function that may be associated during or after treatment are questionable. Therefore, the aim of the present study was to assess the possible alterations in blood parameters and organ function bio markers of sheep that may occur following intramuscular injection of amoxicillin. Amoxicillin has been administered intramuscularly to 10 sheep at a dosage regimen of 7 mg/kg of body weight for 5 successive days. Two types of blood samples (with and without anticoagulant) were collected from the jugular vein pre- and post-administration of the drug. Amoxicillin significantly (P < 0.001) increased total leukocyte count and (P < 0.05) absolute eosinophilic count when compared with those of the control samples. Aspartate aminotransferase, alkaline phosphatase and cholesterol were significantly (P < 0.05) higher than the corresponding control values. In addition, amoxicillin significantly (P < 0.05) increased blood urea nitrogen and creatinine but decreased phosphorus level when compared with those of prior-administration samples. These data may indicate that although the side changes caused by amoxicillin are minor in sheep, yet the liver and kidney functions should be monitored during its usage in therapy and it should be used with care for treatment of sheep with renal and/or hepatic impairments.

Keywords: amoxicillin, biogram, haemogram, sheep

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Authors: Hatem A. El-Mezayen, Ahmed Abdelmajeed, Fatehya Metwally, Usama Elsaly, Salwa Atef

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Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of metastatic breast cancer. Methods: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), and CA15.3 were assayed in metastatic breast cancer (MBC) patients (75), non-MBC patients (50) and healthy control (20). Results: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named MBC-CTCs = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1– 510. That function correctly classified 87% of metastatic breast cancer at cut-off value = 0.55. (i.e great than 0.55 indicates patients with metastatic breast cancer and less than 0.55 indicates patients with non-metastatic breast cancer). Conclusion: MBC-CTCs is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer.

Keywords: metastatic breast cancer, circulating tumor cells, cytokeratin, EpiCam

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Authors: Anupuma Raina, Ajay P. Balayan, Prateek Pandya, Pankaj Shrivastava, Uma Kanga, Tulika Seth

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DNA fingerprinting analysis aids in personal identification for forensic purposes and has always been a driving motivation for law enforcement agencies in almost all countries since its inception. The introduction of DNA markers (Y-STR) has allowed for greater precision and higher discriminatory power in forensic testing. A criminal/ person committing crime after bone marrow transplantation is a rare situation but not an impossible one. Keeping such a situation in mind, a study was carried out to find out the best biological sample to be used for personal identification, especially in forensic situation. We choose a female patient (recipient) and a male donor. The pre transplant sample (blood) and post transplant samples (blood, buccal swab, hair roots) were collected from the recipient (patient). The same were compared with the blood sample of the donor using DNA FP technique. Post transplant samples were collected at different interval of time (15, 30, 60, and 90 days). The study was carried out using Y-STR kit at 23 loci. The results determined discusses the phenomenon of chimerism and its impact on Y-STR. Hair sample was found the most suitable sample which had no donor DNA profiling up to 90 days.

Keywords: bone marrow transplantation, chimerism, DNA profiling, Y-STR

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Authors: Masoud Sheidaei, Fahimeh Koohdar

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Date palms are economically important tree plants with high nutrition and medicinal values. More than 400 date palm cultivars are cultivated in many regions of Iran, but no report is available on landscape genetics and species distribution modeling of these trees from the country. Therefore, the present study provides a detailed insight into the genetic diversity and structure of date palm populations in Iran and investigates the effects of geographical and climatic variables on the structuring of genetic diversity in them. We used different computational methods in the study like, spatial principal components analysis (sPCA), redundancy analysis (RDA), latent factor mixed model (LFMM), and Maxent and Dismo models of species distribution modeling. We used a combination of different molecular markers for this study. The results showed that both global and local spatial features play an important role in the genetic structuring of date palms, and the genetic regions associated with local adaptation and climatic variables were identified. The effects of climatic change on the distribution of these taxa and the genetic regions adaptive to these changes will be discussed.

Keywords: adaptive genetic regions, genetic diversity, isolation by distance, populations divergence

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